Studies are in progress on heart transplantation and transplantation using mouse and rabbit models. Cellular reactivity studies using the direct migration inhibition system have shown sensitization to heart and streptococcal membrane antigens during rejections of hearts transplanted in rabbits. Using the mouse model, animals pretreated with certain concentrations of streptococcal membranes and then transplanted have shown prolonged graft survival with no evidence of cellular sensitization or heart-reactive antibody formation. A fraction of the Group A streptococcal membrane has been isolated which will absorb heart-reactive antibodies. This has been purified to an active fraction of 70,000 daltons which shows 4 bands on SDS polyacrylamide electrophoresis. Cytotoxicity studies are being done using rat heart tissue monolayers to determine if human heart-reactive-antibody per se is cytotoxic. Using sera with this antibody plus complement, heart cells cease to beat within 3-6 hours. Cytotoxicity studies are being done using the Cr51-release method. The cross-reactive membrane fraction will be used for pretreatment before transplantation to find out if this material can result in prolonged graft survival. Studies will be carried out to ascertain whether the failure to react to the transplanted heart is due to specific tolerance or to a general depression of immune responsiveness.